Defined-sequence biopolymers, such as polypeptides and polynucleotides, are routinely synthesized by solid-phase methods in which polymer subunits are added stepwise to a growing polymer chain immobilized on a solid support. The general synthetic procedure can be carried out with commercially available synthesizers which can construct defined sequence biopolymers in an automated or semi-automated fashion. Heretofore, however, commercially available synthesizers have been limited by the total quantity of polymer which can be synthesized in a single operation.
Increasingly, there is an interest in synthesizing biopolymer mixtures containing different-sequence biopolymers. For example, it is often of interest, in examining structure-function relationships in peptides, to generate a mixture of peptides having different amino acid substitutions at one or more defined polypeptide residue positions. As another example, polypeptides having a desired activity, such as a high binding affinity to a given receptor or antibody, may be identified by (a) generating a large number of random-sequence peptides, and (b) screening these peptides to identify one or more peptides having the desired binding affinity. Preferably, the polypeptides in the mixture are present in substantially equimolar amounts, to maximize the possibility of detecting any one sequence out of large number of sequences, and in molar amounts which allow detection of a single sequence.
Although methods have been proposed for synthesizing mixtures of different-sequence peptides (e.g., Houghton, Geysen), such methods are limited in both the number and quantity of different sequence polypeptides which can be synthesized in a single operation, and also are relatively expensive to carry out. These limitations have restricted the availability of different-sequence peptides, both for structure-function studies, or for polypeptide selection methods.